Intuiciones y restricción del principio de cierre.

En este artículo, considero algunos supuestos costos intuitivos relativos a la negación de la generalidad del Principio de Cierre para el conocimiento. Usualmente los filósofos descartan tal negación como altamente contra-intuitiva pero argumento que, por lo menos en relación a los supuestos costos aquí considerados, esto es incorrecto: dadas nuestras intuiciones folk, no hay tales costos. Por lo tanto un falibilista que busca detener el argumento escéptico basado en el principio de cierre puede restringir el principio sin sufrir esos supuestos costos intuitivos.Abstract In this article I consider some alleged intuitive costs concerning the denial of the full generality of the Principle of Closure for knowledge. Usually philosophers dismiss such denial as highly counter-intuitive but I argue that, at least with regard to the alleged costs here considered, this is wrong: given our folk-intuitions, there are no such costs. So a fallibilist who seeks to halt the closure-based sceptical argument can restrict the principle with no such intuitive costs

Jueces e injusticias epistémicas

Las injusticias epistémicas causan un mal a alguien en su condición de sujeto epistémico; es decir, como sujeto que participa en la producción, mantención y transmisión de bienes epistémicos. Asumiendo que una de las metas, pero no ciertamente la única, del sistema judicial es promover decisiones que sean razonablemente plausibles, las injusticias epistémicas interfieren con dicha meta. Un objetivo de este artículo es ofrecer un par de recomendaciones institucionales que contribuyen a disminuir las injusticias epistémicas que los jueces pudieran cometer. Estas recomendaciones se basan en data empírica proveniente de las ciencias sociales. Otro objetivo es argumentar, en parte en base a esas intervenciones, que ni el enfoque individualista ni el estructuralista, que ubican el problema y los cambios necesarios para remediarlo en la mente del individuo o las estructuras de nuestro entorno (respectivamente), son adecuadamente concebidos. En particular, el artículo responde a la pregunta: ¿qué tipo de intervenciones, dada la data empírica disponible, es más probable que sea eficiente?, mostrando que esas intervenciones son híbridas, combinando lo individual y lo estructural, dada la interdependencia de lo individual y lo estructural, y ofreciendo dos ejemplos ilustrativos de distintas estrategias de este tipo de intervenciones

Jueces e injusticias epistémicas: recomendaciones institucionales y la interdependencia de lo individual y lo estructural = Judges and epistemic injustices: institutional recommendations and the interdependence of the individual and the structural

Aborda as injustiças epistêmicas cometidas pelos juízes e discute recomendações institucionais para reduzi-las. O objetivo é fornecer um par de recomendações institucionais baseadas em dados empíricos das ciências sociais, que contribuam para diminuir as injustiças epistêmicas cometidas pelos juízes

A peculiaridade e contingência da introspecção da crença

The Causal Model of introspection has its more than fair share of critics and indeed in recent years the model has fallen out of favor in the philosophical world. In this paper, I defend the model and argue that it is an excellent candidate, given a realist commitment about the mental, to explain our peculiar, but contingent, introspective access to beliefs.Keywords: causal model, introspection, belief, peculiarity of self-ascriptions, contingency of self-ascriptions.O modelo causal de introspecção tem recebido muitas críticas e, de fato, nos últimos anos, tem caído em desuso no mundo filosófico. Neste artigo defendo o modelo e sustento que ele é um excelente candidato, dado um compromisso realista para com o mental, para explicar o nosso acesso introspectivo peculiar, mas contingente, às crenças.Palavras-chave: modelo causal, introspecção, crença, peculiaridade de autoatribuições, contingência de autoatribuições

Incompetência cidadã e estrutura epistêmica da sociedade

The epistemic structure of society, with its division of epistemic and cognitive labour, can help us deal with the citizenry incompetence threat that many contemporary conceptions of democracy suffer as long as a certain intellectual character is possessed by the citizens.Keywords: expert testimony, collective deliberation, intellectual virtue, democracy.A estrutura epistêmica da sociedade, com sua divisão do trabalho epistêmico e cognitivo, pode nos ajudar a lidar com a ameaça da incompetência dos cidadãos que muitas concepções contemporâneas de democracia sofrem, desde que um certo caráter intelectual seja possuído pelos cidadãos.Palavras-chave: testemunho de especialistas, deliberação coletiva, virtude intelectual, democracia

Conhecimento como um tipo social

This paper motivates an account of knowledge as a social kind, following a cue by Edward Craig, which captures two major insights behind social and feminist epistemologies, in particular our epistemic interdependence concerning knowledge and the role of social regulative practices in understanding knowledge.Keywords: epistemic anti-individualism, regulative epistemology, practical explication, testimony.Este artigo motiva um relato do conhecimento como um tipo social, seguindo uma sugestão de Edward Craig, que capta dois grandes pontos de vista das epistemologias sociais e feministas, em particular a nossa interdependência epistêmica em relação ao conhecimento e o papel das práticas reguladoras sociais na compreensão do conhecimento.Palavras-chave: anti-individualismo epistemológico, epistemologia reguladora, explicação prática, testemunho

Eighteen Years of Molecular Genotyping the Hemophilia Inversion Hotspot: From Southern Blot to Inverse Shifting-PCR

The factor VIII gene (F8) intron 22 inversion (Inv22) is a paradigmatic duplicon-mediated rearrangement, found in about one half of patients with severe hemophilia A worldwide. The identification of this prevalent cause of hemophilia was delayed for nine years after the F8 characterization in 1984. The aim of this review is to present the wide diversity of practical approaches that have been developed for genotyping the Inv22 (and related int22h rearrangements) since discovery in 1993. The sequence— Southern blot, long distance-PCR and inverse shifting-PCR—for Inv22 genotyping is an interesting example of scientific ingenuity and evolution in order to resolve challenging molecular diagnostic problems

Tiorredoxina o1 mitocondrial y nuclear : implicación en autofagia, señalización hormonal y en persulfuración bajo estrés salino

Las tiorredoxinas, proteínas de bajo peso molecular, tienen un papel fundamental en el mantenimiento de la homeostasis redox celular. Estas enzimas se caracterizan por presentar un sitio activo conservado (WCGCP) compuesto por dos residuos de cisteína a través del cual regulan la estructura y función de sus proteínas diana específicas mediante reducción de residuos de Cys oxidados en puentes disulfuro. Las diferentes isoformas de las TRXs pueden encontrase en distintos compartimentos celulares. Concretamente, la TRXo1, objeto de estudio de esta Tesis Doctoral, presenta una localización dual, hallándose tanto en mitocondrias como en núcleo, analizándose su implicación en procesos como la autofagia celular y en procesos dependientes de la fitohormona ABA a través de la regulación de nuevas dianas proteicas. Dentro del primer Objetivo propuesto, utilizando como modelos de estudio suspensiones de células de tabaco BY-2 control y sobreexpresantes (OEX) Pstrxo1, se ha estudiado la posible implicación de TRXo1 en la viabilidad celular tras un tratamiento oxidativo con H2O2, a través de la regulación de la proteína ATG4 (Autophagy related protein 4), clave en el proceso de autofagia celular. Como resultado, se observó una elevada actividad de ATG4 en las células OEX sometidas al tratamiento oxidativo, junto con la demostrada interacción in vitro entre las proteínas ATG4 y TRXo1, sugiriendo un papel para esta tiorredoxina en el control redox de la proteína ATG4 in vivo. En este sentido, la TRXo1 se postula como un componente clave en el proceso de autofagia que tiene lugar en la respuesta de las células TBY-2 a la situación oxidativa, colaborando en el aumento de la tasa de supervivencia celular que presentan las células sobreexpresantes. Además, dentro del segundo Objetivo parcial propuesto, se analizó la regulación redox de PYR1 (Pyrabactin Resistance 1), receptor de ABA, mediada por TRXo1 y su implicación en procesos dependientes de esta fitohormona como son el crecimiento de la raíz y el cierre estomático, analizados en mutantes KO y sobreexpresantes (OEX) Attrxo1 de plantas de Arabidopsis thaliana L. ecotipo Columbia, así como en estudios in vitro con proteínas recombinantes de PYR1 wild type y mutadas en sus cisteínas, sometidas a ensayos de óxido-reducción. Se ha demostrado una regulación redox de este receptor que provoca cambios en su estado oligomérico, estando dos de sus tres cisteínas, concretamente Cys30 y Cys65, implicadas en el mismo. A su vez, el sistema tiorredoxina reductasa/ TRXo1 era capaz de rescatar la pérdida de la actividad de PYR1 por oxidación, y de esta forma su capacidad para inhibir a fosfatasas implicadas en la señalización por ABA, como es la proteína HAB1. Los estudios in vivo han corroborado que la oligomerización de PYR1 es dependiente del estado redox, encontrándose además un patrón diferencial en la oligomerización del receptor en plantas KO y sobreexpresantes Attrxo1 crecidas en presencia de ABA, comparadas con el patrón presentado por el genotipo silvestre. Todo ello permite describir por vez primera, la implicación del proceso de regulación redox por TRXo1 sobre el receptor PYR1, que puede ser un evento clave para favorecer la señalización por ABA, siendo esta tiorredoxina una buena candidata como reductor fisiológico in vivo de estos receptores en el núcleo. También, se estudia la participación de AtTRXo1 en procesos de persulfuración proteica (Objetivo 3), modificación postraduccional sobre residuos de Cys, en plantas mutantes knock out (KO) y sobreexpresantes (OEX) Attrxo1 crecidas bajo condiciones de estrés salino, presentándose por primera vez un estudio sobre patrones de persulfuración proteica producida por sulfuro de hidrógeno (H2S) en condiciones de salinidad, en el que algunas dianas de TRXo1 en mitocondrias y núcleo, así como proteínas del sistema antioxidante y del metabolismo del H2S entre otras, se encuentran diferencialmente persulfuradas en mutantes KO Attrxo1. Este patrón sugiere que TRXo1 puede ejercer un papel como posible moduladora del proceso de persulfuración en estas condiciones de estrés abiótico, aspecto interesante en el que se ahondará próximamente. Por otro lado, se han obtenido dobles mutantes de Tiorredoxina Reductasa B (NTRB) y de TRXo1 (Psntrb/trxo1) de Pisum sativum L. cv. Bonneville, por la técnica de silenciamiento génico inducido por virus (VIGS) y de A. thaliana (Attrxo1/ntrb) por cruzamiento de mutantes simples KO en cada uno de los genes (Objetivo 4). Se ha iniciado la caracterización de los mismos como paso previo a su empleo en los estudios dirigidos a profundizar en la participación de la regulación redox ejercida por este sistema, en la respuesta de plantas a situaciones de estrés abiótico, donde la TRXo1 tiene un papel que se evidencia cada vez más, como relevante.Thioredoxins, low molecular weight proteins, play a fundamental role in the maintenance of cellular redox homeostasis. These enzymes are characterized by a conserved active site (WCGCP) composed of two cysteine residues through which they regulate the structure and function of their specific target proteins by reducing oxidized Cys residues in disulfide bridges. The different isoforms of TRXs can be found in different cellular compartments. Specifically, TRXo1, the object of study of this Doctoral Thesis, presents a dual localization, being found both in mitochondria and in the nucleus, and its involvement in processes such as cell autophagy and in processes dependent on the phytohormone ABA through the regulation of new protein targets is being analyzed. Within the first proposed Objective, using as study models suspensions of BY-2 control and overexpressing (OEX) Pstrxo1 tobacco cells, we have studied the possible involvement of TRXo1 in cell viability after oxidative treatment with H2O2, through the regulation of the ATG4 protein (Autophagy related protein 4), key in the process of cellular autophagy. As a result, elevated ATG4 activity was observed in OEX cells subjected to oxidative treatment, together with the demonstrated in vitro interaction between ATG4 and TRXo1 proteins, suggesting a role for this thioredoxin in the redox control of ATG4 protein in vivo. In this sense, TRXo1 is postulated as a key component in the autophagy process that takes place in the response of TBY-2 cells to the oxidative situation, collaborating in the increase of the cell survival rate presented by overexpressing cells. In addition, within the second proposed partial Objective, the redox regulation of PYR1 (Pyrabactin Resistance 1), ABA receptor, mediated by TRXo1 and its implication in processes dependent on this phytohormone such as root growth and stomatal closure, were analyzed in KO mutants and Attrxo1 overexpressing (OEX) of Arabidopsis thaliana L. ecotype Columbia, as well as in vitro studies with wild-type and cysteine-mutated PYR1 recombinant proteins subjected to oxidation-reduction assays. A redox regulation of this receptor that causes changes in its oligomeric state has been demonstrated, with two of its three cysteines, specifically Cys30 and Cys65, being involved in it. In turn, the thioredoxin reductase/ TRXo1 system was capable of rescuing the loss of PYR1 activity by oxidation, and thus its capacity to inhibit phosphatases involved in ABA signaling, such as the HAB1 protein. In vivo studies have corroborated that PYR1 oligomerization is redox state-dependent, and a differential pattern of receptor oligomerization was found in KO and Attrxo1 overexpressing plants grown in the presence of ABA, compared with the pattern presented by the wild-type genotype. All this allows us to describe for the first time, the involvement of the redox regulation process by TRXo1 on the PYR1 receptor, which may be a key event to favor ABA signaling, being this thioredoxin a good candidate as a physiological reductant in vivo of these receptors in the nucleus. Also, the participation of AtTRXo1 in protein persulfuration processes (Objective 3), posttranslational modification on Cys residues, is studied in Attrxo1 knock-out (KO) and overexpressing (OEX) mutant plants grown under salt stress conditions, presenting for the first time a study on patterns of protein persulfuration produced by hydrogen sulfide (H2S) under salinity conditions, in which some TRXo1 targets in mitochondria and nucleus, as well as proteins of the antioxidant system and H2S metabolism, among others, are differentially persulfurated in KO Attrxo1 mutants. This pattern suggests that TRXo1 may play a role as a possible modulator of the persulfuration process under these abiotic stress conditions, an interesting aspect that will be further explored in the near future. On the other hand, double mutants of Thioredoxin Reductase B (NTRB) and TRXo1 (Psntrb/trxo1) have been obtained from Pisum sativum L. cv. Bonneville, by virus-induced gene silencing technique (VIGS) and of A. thaliana (Attrxo1/ntrb) by crossing KO single mutants in each of the genes (Objective 4). The characterization of these genes has been initiated as a previous step to their use in studies aimed at deepening the participation of the redox regulation exerted by this system in the response of plants to abiotic stress situations, where TRXo1 has a role that is increasingly evidenced as relevan

Therapeutic approach to bronchiolitis: why pediatricians continue to overprescribe drugs?

<p>Abstract</p> <p>Background</p> <p>Bronchiolitis guidelines suggest that neither bronchodilators nor corticosteroids, antiviral and antibacterial agents should be routinely used. Although recommendations, many clinicians persistently prescribe drugs for bronchiolitis.</p> <p>Aim of the study</p> <p>To unravel main reasons of pediatricians in prescribing drugs to infants with bronchiolitis, and to possibly correlate therapeutic choices to the severity of clinical presentation. Also possible influence of socially deprived condition on therapeutic choices is analyzed.</p> <p>Methods</p> <p>Patients admitted to Pediatric Division of 2 main Hospitals of Naples because of bronchiolitis in winter season 2008-2009 were prospectively analyzed. An RDAI (Respiratory Distress Assessment Instrument) score was assessed at different times from admission. Enrolment criteria were: age 1-12 months; 1^stlower respiratory infection with cough and rhinitis with/without fever, wheezing, crackles, tachypnea, use of accessory muscles, and/or nasal flaring, low oxygen saturation, cyanosis. Social deprivation status was assessed by evaluating school graduation level of the origin area of the patients. A specific questionnaire was submitted to clinicians to unravel reasons of their therapeutic behavior.</p> <p>Results</p> <p>Eighty-four children were enrolled in the study. Mean age was 3.5 months. Forty-four per cent of patients presented with increased respiratory rate, 70.2% with chest retractions, and 7.1% with low SaO2. Mean starting RDAI score was 8. Lung consolidation was found in 3.5% on chest roentgenogram. Data analysis also unraveled that 64.2% matched clinical admission criteria. Social deprivation status analysis revealed that 72.6% of patients were from areas "at social risk". Evaluation of length of stay vs. social deprivation status evidenced no difference between "at social risk" and "not at social risk" patients. Following therapeutic interventions were prescribed: nasal suction (64.2%), oxygen administration (7.1%), antibiotics (50%), corticosteroids (85.7%), bronchodilators (91.6%). Statistically significant association was not found for any used drug with neither RDAI score nor social deprivation status. The reasons of hospital pediatricians to prescribe drugs were mainly the perception of clinical severity of the disease, the clinical findings at chest examination, and the detection of some improvement after drug administration.</p> <p>Conclusions</p> <p>We strongly confirm the large use of drugs in bronchiolitis management by hospital pediatricians. Main reason of this wrong practice appears to be the fact that pediatricians recognize bronchiolitis as a severe condition, with consequent anxiety in curing so acutely ill children without drugs, and that sometimes they feel forced to prescribe drugs because of personal reassurance or parental pressure. We also found that social "at risk" condition represents a main reason for hospitalization, not correlated to clinical severity of the disease neither to drug prescription. Eventually, we suggest a "step-by-step" strategy to rich a more evidence based approach to bronchiolitis therapy, by adopting specific and shared resident guidelines.</p